4-benzyloxy-2 (1h)-pyridones

ABSTRACT

Preparation of 4-benzyloxy-2(1H)-pyridones and their antimicrobial activity are disclosed.

United States Patent 1 [111 3,853,900 Shone Dec, 10, 1974 4-BENZYLOXY-2 (lH)-PYRIDONES OTHER PUBLICATIONS [75] Inventor: Robert L. Shone, Palatine, Ill. Wenner et a!" Chema Abstracts, VOL 41 [73] Assignee: G. D. Searle and Co., Chicago, Ill. 1675d1676C,

Wenner et al., Chem. Abstracts, Vol. 41, 5904e-i, [22] Filed. Sept. 14, 1973 I 21 Appl. No.: 397,233

. Primary Examiner-Alan L. Rotman 52 us. Cl. 260/297 2, 424/263 Attorney, Agent or Firm-John Brown [51] Int. Cl C07d 31/30 [58] Field of Search 260/297 Z 57 ABSTRACT [56] References Cited Preparation of 4-benzyloxy-2( ll'l)-pyridones and their antimicrobial activity are disclosed. UNITED STATES PATENTS 2,414,783 1/ 1947 4 Claims, No Drawings Wenner et al 260/297 Z 1 4-BENZYLOXY-2 (lH)-PYRIDONES This invention relates to 4-ben2yloxy-2(ll-l)- pyridones and a process for the preparation thereof. More particularly, this invention provides new, useful,

and unobvious chemical compounds of the formula I O R OCH2 wherein R represents hydrogen or methyl ortho to the benzyloxy.

The compounds to which this invention relates are useful by reason of their valuable biological properties. Thus, for example, they are antimicrobial agents especially but not exclusively adapted to inhibit the growth of bacteria, protozoa, and fungi. In standardized tests for such activity versus Erwinia sp., Tetrahymena pyriformis, Trichophylon mentagrophytes, and Verticillium albo-atrum, the compounds of this invention were found effective in concentrations of 1,000 mcgm. per ml.

Those skilled in the art will recognize that observations of activity in standardized tests for particular biological effects are fundamental to the development of valuable new drugs, both veterinary and human.

Preparation of the instant compounds proceeds by heating a pyridine l-oxide of the formula OCH-l with acetic anhydride, and heating the resultant intermediate with methanol in ethyl acetate.

The following examples describe in detail compounds illustrative of the present invention and methods which have been devised for their preparation. It will be apparent to those skilled in the art that many modifications, both of materials and of methods, may be practiced without departing from the purpose and intent of this disclosure. Throughout the examples hereinafter set forth, temperatures are given in degrees centigrade and relative amounts of materials in parts by weight, except as otherwise noted.

EXAMPLE 1 4-Benzyloxy-2( lH)-pyridone A mixture of 185 parts of 4-benzyloxypyridine-loxide and 1,100 parts of acetic anhydride is heated at the boiling point under reflux for 2 hours, whereupon EXAMPLE 2 v 4-Benzyloxy-3-methyl-2( 1H )-pyridone and 4-benzyloxy-5-methyl-2( lH)-pyridone A mixture of 97 parts of 4-benzyloxy-3- methylpyridine l-oxide and 400 parts of acetic anhydride is heated at the boiling point under reflux for 3 hours. The anhydride is thereupon removed by vacuum distillation, and the dark residue is extracted with 450 parts of ethyl acetate. A small amount of insoluble material is removed by filtration. The filtrate is mixed with approximately 25 parts of methanol, and the resultant solution is heated at the boiling point under reflux for 5 minutes. Solvent is stripped by vacuum distillation, and the dark residue is dissolved in chloroform. The chloroform solution is chromatographed on silica gel, using chloroform and then a 1 percent solution of ethanol in chloroform as developing solvents. From the primarly ethanol-chloroform eluates, on evaporation of solvent, 4-benzyloxy-3-methyl-2( lH)-pyridone melting at approximately 2l4-215 is obtained. Subsequent ethanolchloroform eluates, on evaporation of solvent, afford 4-benz'yloxy-5-methyl-2( lH)-pyridone melting in the range l45l50.

What is claimed is:

l. A compound of the formula OCH wherein R represents hydrogen or methyl ortho to the benzyloxy.

2. A compound according to claim 1 which is 4-benzyloxy-2( 1H )-pyridone.

'. 3. A compound according to claim 1 which is 4- benzyloxy-3-methyl-2( 1 H )-pyridone.

4. A compound according to claim 1 which is 4- benzyloxy-5-methyl-2( 1H )-pyridone. 

1. A COMPOUND OF THE FORMULA
 2. A compound according to claim 1 which is 4-benzyloxy-2(1H)-pyridone.
 3. A compound according to claim 1 which is 4-benzyloxy-3-methyl-2(1H)-pyridone.
 4. A compound according to claim 1 which is 4-benzyloxy-5-methyl-2(1H)-pyridone. 